Pub Date : 2024-11-05DOI: 10.1177/0271678X241298584
Praveena Elanghovan, Thanh Nguyen, Pascal Spincemaille, Ajay Gupta, Yi Wang, Junghun Cho
The study investigated the sensitivity of a novel MRI-based OEF mapping, quantitative susceptibility mapping plus quantitative blood oxygen level-dependent imaging (QSM+qBOLD or QQ), to physiological changes, particularly increased oxygen extraction fraction (OEF) by using hyperventilation as a vasoconstrictive stimulus. While QQ's sensitivity to decreased OEF during hypercapnia has been demonstrated, its sensitivity to increased OEF levels, crucial for cerebrovascular disorders like vascular dementia and Parkinson's disease, remains unexplored. In comparison with a previous QSM-based OEF, we evaluated QQ's sensitivity to high OEF values. MRI data were obtained from 11 healthy subjects during resting state (RS) and hyperventilation state (HV) using a 3 T MRI with a three-dimensional multi-echo gradient echo sequence (mGRE) and arterial spin labeling (ASL). Region of interest (ROI) analysis and paired t-tests were used to compare OEF, CMRO2 and CBF between QQ and QSM. Similar to QSM, QQ showed higher OEF during HV compared to RS: in cortical gray matter, QQ-OEF and QSM-OEF was 36.44.7% and 35.312.5% at RS and 45.011.6% and 45.014.8% in HV, respectively. These findings demonstrate QQ's ability to detect physiological changes and suggest its potential in studying brain metabolism in neurological disorders.
{"title":"Sensitivity assessment of QSM+qBOLD (or QQ) in detecting elevated oxygen extraction fraction (OEF) in physiological change.","authors":"Praveena Elanghovan, Thanh Nguyen, Pascal Spincemaille, Ajay Gupta, Yi Wang, Junghun Cho","doi":"10.1177/0271678X241298584","DOIUrl":"https://doi.org/10.1177/0271678X241298584","url":null,"abstract":"<p><p>The study investigated the sensitivity of a novel MRI-based OEF mapping, quantitative susceptibility mapping plus quantitative blood oxygen level-dependent imaging (QSM+qBOLD or QQ), to physiological changes, particularly increased oxygen extraction fraction (OEF) by using hyperventilation as a vasoconstrictive stimulus. While QQ's sensitivity to decreased OEF during hypercapnia has been demonstrated, its sensitivity to increased OEF levels, crucial for cerebrovascular disorders like vascular dementia and Parkinson's disease, remains unexplored. In comparison with a previous QSM-based OEF, we evaluated QQ's sensitivity to high OEF values. MRI data were obtained from 11 healthy subjects during resting state (RS) and hyperventilation state (HV) using a 3 T MRI with a three-dimensional multi-echo gradient echo sequence (mGRE) and arterial spin labeling (ASL). Region of interest (ROI) analysis and paired t-tests were used to compare OEF, CMRO<sub>2</sub> and CBF between QQ and QSM. Similar to QSM, QQ showed higher OEF during HV compared to RS: in cortical gray matter, QQ-OEF and QSM-OEF was 36.4<math><mo> </mo><mo>±</mo><mo> </mo></math>4.7% and 35.3<math><mo> </mo><mo>±</mo><mo> </mo></math>12.5% at RS and 45.0<math><mo> </mo><mo>±</mo><mo> </mo></math>11.6% and 45.0<math><mo> </mo><mo>±</mo><mo> </mo></math>14.8% in HV, respectively. These findings demonstrate QQ's ability to detect physiological changes and suggest its potential in studying brain metabolism in neurological disorders.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-05DOI: 10.1177/0271678X241296799
Takuma Nishimoto, Fumiaki Oka, Takao Inoue, Hiroshi Moriyama, Reo Kawano, Michiyasu Suzuki, David Y Chung, Cenk Ayata, Hideyuki Ishihara
Spreading depolarization (SD) develops after stroke and traumatic brain injury and may contribute to secondary brain damage. These diseases are often accompanied by intracranial hypertension, but little is known about the effects of intracranial pressure (ICP) on SD. Here, we study the effect of increased ICP on hemodynamic and metabolic response to SD in rats. SDs were triggered at different ICPs and cerebral perfusion pressures (CPP). The regional cerebral blood flow (rCBF), partial pressure of brain tissue oxygen (PbtO2), cerebral extracellular glucose and lactate concentrations were recorded. Fluoro-Jade staining was used to quantify neuronal injury in cortex. At high ICP (50 mmHg) with low CPP (30 mmHg), rCBF and PbtO2 were monophasically decreased in contrast to a monophasically increased pattern under normal conditions. Neuronal death increased in both hemispheres but much more on the side where SDs were triggered. At high ICP (50 mmHg) with normal CPP (70 mmHg), CBF and metabolism during SD did not differ from baseline, and neuronal death did not increase even on the side of SD induction. These data suggest that maintaining CPP at 70 mmHg, even when the ICP is as high as 50 mmHg, preserves normal blood flow and metabolism during SD events and prevents neuronal degeneration.
{"title":"Impact of intracranial hypertension and cerebral perfusion pressure on spreading depolarization.","authors":"Takuma Nishimoto, Fumiaki Oka, Takao Inoue, Hiroshi Moriyama, Reo Kawano, Michiyasu Suzuki, David Y Chung, Cenk Ayata, Hideyuki Ishihara","doi":"10.1177/0271678X241296799","DOIUrl":"https://doi.org/10.1177/0271678X241296799","url":null,"abstract":"<p><p>Spreading depolarization (SD) develops after stroke and traumatic brain injury and may contribute to secondary brain damage. These diseases are often accompanied by intracranial hypertension, but little is known about the effects of intracranial pressure (ICP) on SD. Here, we study the effect of increased ICP on hemodynamic and metabolic response to SD in rats. SDs were triggered at different ICPs and cerebral perfusion pressures (CPP). The regional cerebral blood flow (rCBF), partial pressure of brain tissue oxygen (PbtO<sub>2</sub>), cerebral extracellular glucose and lactate concentrations were recorded. Fluoro-Jade staining was used to quantify neuronal injury in cortex. At high ICP (50 mmHg) with low CPP (30 mmHg), rCBF and PbtO2 were monophasically decreased in contrast to a monophasically increased pattern under normal conditions. Neuronal death increased in both hemispheres but much more on the side where SDs were triggered. At high ICP (50 mmHg) with normal CPP (70 mmHg), CBF and metabolism during SD did not differ from baseline, and neuronal death did not increase even on the side of SD induction. These data suggest that maintaining CPP at 70 mmHg, even when the ICP is as high as 50 mmHg, preserves normal blood flow and metabolism during SD events and prevents neuronal degeneration.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-02DOI: 10.1177/0271678X241291958
Ylenia Giarratano, Elizabeth A Hill, Charlene Hamid, Stewart Wiseman, Calum Gray, Francesca M Chappell, Roberto Duarte Coello, Maria C Valdés-Hernández, Lucia Ballerini, Michael S Stringer, Michael J Thrippleton, Daniela Jaime Garcia, Xiaodi Liu, William Hewins, Yajun Cheng, Sandra E Black, Andrew Lim, Rosa Sommer, Joel Ramirez, Bradley J MacIntosh, Rosalind Brown, Fergus Doubal, Tom MacGillivray, Joanna M Wardlaw, Renata Riha, Miguel O Bernabeu
Optical coherence tomography angiography (OCT-A) retinal imaging enables in vivo visualization of the retinal microvasculature that is developmentally related to the brain and can offer insight on cerebrovascular health. We investigated retinal phenotypes and neuroimaging markers of small vessel disease (SVD) in individuals with obstructive sleep apnoea (OSA). We enrolled 44 participants (mean age 50.1 ± SD 9.1 years) and performed OCT-A imaging before and after continuous positive airway pressure (CPAP) therapy. Pre-treatment analyses using a generalized estimating equations model adjusted for relevant covariates, revealed perivascular spaces (PVS) volume in basal ganglia associated with greater foveal vessel density (fVD) (p-value < 0.001), and smaller foveal avascular zone area (p-value = 0.01), whereas PVS count in centrum semiovale associated with lower retinal vessel radius (p-value = 0.02) and higher vessel tortuosity (p-value = 0.01). A reduction in retinal vessel radius was also observed with increased OSA severity (p-value = 0.05). Post-treatment analyses showed greater CPAP usage was associated with a decrease in fVD (p-value = 0.02), and increased retinal vessel radius (p-value = 0.01). The findings demonstrate for the first time the potential use of OCT-A to monitor CPAP treatment and its possible impact on both retinal and brain vascular health.
{"title":"Retinal microvascular phenotypes can track small vessel disease burden and CPAP treatment effectiveness in obstructive sleep apnoea.","authors":"Ylenia Giarratano, Elizabeth A Hill, Charlene Hamid, Stewart Wiseman, Calum Gray, Francesca M Chappell, Roberto Duarte Coello, Maria C Valdés-Hernández, Lucia Ballerini, Michael S Stringer, Michael J Thrippleton, Daniela Jaime Garcia, Xiaodi Liu, William Hewins, Yajun Cheng, Sandra E Black, Andrew Lim, Rosa Sommer, Joel Ramirez, Bradley J MacIntosh, Rosalind Brown, Fergus Doubal, Tom MacGillivray, Joanna M Wardlaw, Renata Riha, Miguel O Bernabeu","doi":"10.1177/0271678X241291958","DOIUrl":"https://doi.org/10.1177/0271678X241291958","url":null,"abstract":"<p><p>Optical coherence tomography angiography (OCT-A) retinal imaging enables <i>in vivo</i> visualization of the retinal microvasculature that is developmentally related to the brain and can offer insight on cerebrovascular health. We investigated retinal phenotypes and neuroimaging markers of small vessel disease (SVD) in individuals with obstructive sleep apnoea (OSA). We enrolled 44 participants (mean age 50.1 ± SD 9.1 years) and performed OCT-A imaging before and after continuous positive airway pressure (CPAP) therapy. Pre-treatment analyses using a generalized estimating equations model adjusted for relevant covariates, revealed perivascular spaces (PVS) volume in basal ganglia associated with greater foveal vessel density (fVD) (p-value < 0.001), and smaller foveal avascular zone area (p-value = 0.01), whereas PVS count in centrum semiovale associated with lower retinal vessel radius (p-value = 0.02) and higher vessel tortuosity (p-value = 0.01). A reduction in retinal vessel radius was also observed with increased OSA severity (p-value = 0.05). Post-treatment analyses showed greater CPAP usage was associated with a decrease in fVD (p-value = 0.02), and increased retinal vessel radius (p-value = 0.01). The findings demonstrate for the first time the potential use of OCT-A to monitor CPAP treatment and its possible impact on both retinal and brain vascular health.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-05-13DOI: 10.1177/0271678X241254680
Ana Monteiro, Pedro Castro, Gilberto Pereira, Carmen Ferreira, Jorge Polonia, Mariana Lobo, Elsa Azevedo
We examined the relation between transcranial Doppler (TCD) markers of cerebral blood flow regulation and cognitive performance in hypertension (HT) patients to evaluate the predictive value of these markers for cognitive decline. We assessed dynamic cerebral autoregulation (dCA), vasoreactivity to carbon dioxide, and neurovascular coupling (NVC) in the middle (MCA) and posterior (PCA) cerebral arteries of 52 patients. Neuropsychological evaluation included the Montreal Cognitive Assessment and tests covering attention, executive function, processing speed, and memory. Notably, reduced rate time in the PCA significantly predicted better processing speed (p = 0.003). Furthermore, reduced overshoot systolic cerebral blood velocity in the PCA and reduced phase in the VLF range in the MCA (p = 0.021 and p = 0.017, respectively) significantly predicted better memory. Intriguingly, enhanced dCA in the MCA predicted poorer memory performance, while reduced NVC in the PCA predicted both superior processing speed and memory performance. These findings suggest that HT-induced changes in cerebral hemodynamics impact cognitive performance. Further research should verify these observations and elucidate whether these changes represent adaptive responses or neurovascular inefficiency. TCD markers might provide insights into HT-related cognitive decline.
{"title":"Cerebral blood flow regulation and cognitive performance in hypertension.","authors":"Ana Monteiro, Pedro Castro, Gilberto Pereira, Carmen Ferreira, Jorge Polonia, Mariana Lobo, Elsa Azevedo","doi":"10.1177/0271678X241254680","DOIUrl":"10.1177/0271678X241254680","url":null,"abstract":"<p><p>We examined the relation between transcranial Doppler (TCD) markers of cerebral blood flow regulation and cognitive performance in hypertension (HT) patients to evaluate the predictive value of these markers for cognitive decline. We assessed dynamic cerebral autoregulation (dCA), vasoreactivity to carbon dioxide, and neurovascular coupling (NVC) in the middle (MCA) and posterior (PCA) cerebral arteries of 52 patients. Neuropsychological evaluation included the Montreal Cognitive Assessment and tests covering attention, executive function, processing speed, and memory. Notably, reduced rate time in the PCA significantly predicted better processing speed (<i>p = </i>0.003). Furthermore, reduced overshoot systolic cerebral blood velocity in the PCA and reduced phase in the VLF range in the MCA (<i>p = </i>0.021 and <i>p = </i>0.017, respectively) significantly predicted better memory. Intriguingly, enhanced dCA in the MCA predicted poorer memory performance, while reduced NVC in the PCA predicted both superior processing speed and memory performance. These findings suggest that HT-induced changes in cerebral hemodynamics impact cognitive performance. Further research should verify these observations and elucidate whether these changes represent adaptive responses or neurovascular inefficiency. TCD markers might provide insights into HT-related cognitive decline.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-06-17DOI: 10.1177/0271678X241261771
Ingeborg Rasing, Naomi Vlegels, Manon R Schipper, Sabine Voigt, Emma A Koemans, Kanishk Kaushik, Rosemarie van Dort, Thijs W van Harten, Alberto De Luca, Ellis S van Etten, Erik W van Zwet, Mark A van Buchem, Huub Am Middelkoop, Geert Jan Biessels, Gisela M Terwindt, Matthias Jp van Osch, Marianne Aa van Walderveen, Marieke Jh Wermer
Peak width of skeletonized mean diffusivity (PSMD) is an emerging diffusion-MRI based marker to study subtle early alterations to white matter microstructure. We assessed PSMD over the clinical continuum in Dutch-type hereditary CAA (D-CAA) and its association with other CAA-related MRI-markers and cognitive symptoms. We included (pre)symptomatic D-CAA mutation-carriers and calculated PSMD from diffusion-MRI data. Associations between PSMD-levels, cognitive performance and CAA-related MRI-markers were assessed with linear regression models. We included 59 participants (25/34 presymptomatic/symptomatic; mean age 39/58 y). PSMD-levels increased with disease severity and were higher in symptomatic D-CAA mutation-carriers (median [range] 4.90 [2.77-9.50]mm2/s × 10-4) compared with presymptomatic mutation-carriers (2.62 [1.96-3.43]mm2/s × 10-4) p = <0.001. PSMD was positively correlated with age, CAA-SVD burden on MRI (adj.B [confidence interval] = 0.42 [0.16-0.67], p = 0.002), with number of cerebral microbleeds (adj.B = 0.30 [0.08-0.53], p = 0.009), and with both deep (adj.B = 0.46 [0.22-0.69], p = <0.001) and periventricular (adj.B = 0.38 [0.13-0.62], p = 0.004) white matter hyperintensities. Increasing PSMD was associated with decreasing Trail Making Test (TMT)-A performance (B = -0.42 [-0.69-0.14], p = 0.04. In D-CAA mutation-carriers microstructural white matter damage is associated with disease phase, CAA burden on MRI and cognitive impairment as reflected by a decrease in information processing speed. PSMD, as a global measure of alterations to the white matter microstructure, may be a useful tool to monitor disease progression in CAA.
{"title":"Microstructural white matter damage on MRI is associated with disease severity in Dutch-type cerebral amyloid angiopathy.","authors":"Ingeborg Rasing, Naomi Vlegels, Manon R Schipper, Sabine Voigt, Emma A Koemans, Kanishk Kaushik, Rosemarie van Dort, Thijs W van Harten, Alberto De Luca, Ellis S van Etten, Erik W van Zwet, Mark A van Buchem, Huub Am Middelkoop, Geert Jan Biessels, Gisela M Terwindt, Matthias Jp van Osch, Marianne Aa van Walderveen, Marieke Jh Wermer","doi":"10.1177/0271678X241261771","DOIUrl":"10.1177/0271678X241261771","url":null,"abstract":"<p><p>Peak width of skeletonized mean diffusivity (PSMD) is an emerging diffusion-MRI based marker to study subtle early alterations to white matter microstructure. We assessed PSMD over the clinical continuum in Dutch-type hereditary CAA (D-CAA) and its association with other CAA-related MRI-markers and cognitive symptoms. We included (pre)symptomatic D-CAA mutation-carriers and calculated PSMD from diffusion-MRI data. Associations between PSMD-levels, cognitive performance and CAA-related MRI-markers were assessed with linear regression models. We included 59 participants (25/34 presymptomatic/symptomatic; mean age 39/58 y). PSMD-levels increased with disease severity and were higher in symptomatic D-CAA mutation-carriers (median [range] 4.90 [2.77-9.50]mm<sup>2</sup>/s × 10<sup>-4</sup>) compared with presymptomatic mutation-carriers (2.62 [1.96-3.43]mm<sup>2</sup>/s × 10<sup>-4</sup>) p = <0.001. PSMD was positively correlated with age, CAA-SVD burden on MRI (adj.B [confidence interval] = 0.42 [0.16-0.67], p = 0.002), with number of cerebral microbleeds (adj.B = 0.30 [0.08-0.53], p = 0.009), and with both deep (adj.B = 0.46 [0.22-0.69], p = <0.001) and periventricular (adj.B = 0.38 [0.13-0.62], p = 0.004) white matter hyperintensities. Increasing PSMD was associated with decreasing Trail Making Test (TMT)-A performance (B = -0.42 [-0.69-0.14], p = 0.04. In D-CAA mutation-carriers microstructural white matter damage is associated with disease phase, CAA burden on MRI and cognitive impairment as reflected by a decrease in information processing speed. PSMD, as a global measure of alterations to the white matter microstructure, may be a useful tool to monitor disease progression in CAA.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-05-21DOI: 10.1177/0271678X241255599
Carlo Perego, Francesca Fumagalli, Francesca Motta, Marianna Cerrato, Edoardo Micotti, Davide Olivari, Daria De Giorgio, Giulia Merigo, Angelo Di Clemente, Alessandra Mandelli, Gianluigi Forloni, Luigi Cervo, Roberto Furlan, Roberto Latini, Robert W Neumar, Giuseppe Ristagno
Cardiac arrest (CA) is one of the leading causes of death worldwide. Due to hypoxic ischemic brain injury, CA survivors may experience variable degrees of neurological dysfunction. This study, for the first time, describes the progression of CA-induced neuropathology in the rat. CA rats displayed neurological and exploratory deficits. Brain MRI revealed cortical and striatal edema at 3 days (d), white matter (WM) damage in corpus callosum (CC), external capsule (EC), internal capsule (IC) at d7 and d14. At d3 a brain edema significantly correlated with neurological score. Parallel neuropathological studies showed neurodegeneration, reduced neuronal density in CA1 and hilus of hippocampus at d7 and d14, with cells dying at d3 in hilus. Microgliosis increased in cortex (Cx), caudate putamen (Cpu), CA1, CC, and EC up to d14. Astrogliosis increased earlier (d3 to d7) in Cx, Cpu, CC and EC compared to CA1 (d7 to d14). Plasma levels of neurofilament light (NfL) increased at d3 and remained elevated up to d14. NfL levels at d7 correlated with WM damage. The study shows the consequences up to 14d after CA in rats, introducing clinically relevant parameters such as advanced neuroimaging and blood biomarker useful to test therapeutic interventions in this model.
心脏骤停(CA)是导致全球死亡的主要原因之一。由于缺氧缺血性脑损伤,心脏骤停幸存者可能会出现不同程度的神经功能障碍。本研究首次描述了 CA 引起的大鼠神经病理学进展。CA 大鼠表现出神经和探索功能障碍。脑磁共振成像显示,大鼠3天(d)时皮质和纹状体水肿,7天(d7)和14天(d14)时胼胝体(CC)、外囊(EC)和内囊(IC)的白质(WM)受损。d3 脑水肿与神经系统评分明显相关。同时进行的神经病理学研究显示,d7和d14时,神经变性、海马CA1和后部神经元密度降低,d3时后部细胞死亡。皮质(Cx)、尾状核丘脑(Cpu)、CA1、CC和EC的小胶质细胞增多,直至d14。Cx、Cpu、CC和EC的星形胶质细胞增多(d3至d7)早于CA1(d7至d14)。血浆中的神经丝光(NfL)水平在d3时升高,并在d14时保持升高。d7 的 NfL 水平与 WM 损伤相关。该研究显示了大鼠CA发生后14天内的后果,引入了临床相关参数,如先进的神经影像学和血液生物标记物,有助于在该模型中测试治疗干预措施。
{"title":"Evolution of brain injury and neurological dysfunction after cardiac arrest in the rat - A multimodal and comprehensive model.","authors":"Carlo Perego, Francesca Fumagalli, Francesca Motta, Marianna Cerrato, Edoardo Micotti, Davide Olivari, Daria De Giorgio, Giulia Merigo, Angelo Di Clemente, Alessandra Mandelli, Gianluigi Forloni, Luigi Cervo, Roberto Furlan, Roberto Latini, Robert W Neumar, Giuseppe Ristagno","doi":"10.1177/0271678X241255599","DOIUrl":"10.1177/0271678X241255599","url":null,"abstract":"<p><p>Cardiac arrest (CA) is one of the leading causes of death worldwide. Due to hypoxic ischemic brain injury, CA survivors may experience variable degrees of neurological dysfunction. This study, for the first time, describes the progression of CA-induced neuropathology in the rat. CA rats displayed neurological and exploratory deficits. Brain MRI revealed cortical and striatal edema at 3 days (d), white matter (WM) damage in corpus callosum (CC), external capsule (EC), internal capsule (IC) at d7 and d14. At d3 a brain edema significantly correlated with neurological score. Parallel neuropathological studies showed neurodegeneration, reduced neuronal density in CA1 and hilus of hippocampus at d7 and d14, with cells dying at d3 in hilus. Microgliosis increased in cortex (Cx), caudate putamen (Cpu), CA1, CC, and EC up to d14. Astrogliosis increased earlier (d3 to d7) in Cx, Cpu, CC and EC compared to CA1 (d7 to d14). Plasma levels of neurofilament light (NfL) increased at d3 and remained elevated up to d14. NfL levels at d7 correlated with WM damage. The study shows the consequences up to 14d after CA in rats, introducing clinically relevant parameters such as advanced neuroimaging and blood biomarker useful to test therapeutic interventions in this model.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141069674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-06-11DOI: 10.1177/0271678X241260629
Jan Oltmer, Hendrik Mattern, Julia Beck, Renat Yakupov, Steven M Greenberg, Jaco Jm Zwanenburg, Tine Arts, Emrah Düzel, Susanne J van Veluw, Stefanie Schreiber, Valentina Perosa
Enlarged perivascular spaces (EPVS) are common in cerebral small vessel disease (CSVD) and have been identified as a marker of dysfunctional brain clearance. However, it remains unknown if the enlargement occurs predominantly around arteries or veins. We combined in vivo ultra-high-resolution MRI and histopathology to investigate the spatial relationship of veins and arteries with EPVS within the basal ganglia (BG). Furthermore, we assessed the relationship between the EPVS and measures of blood-flow (blood-flow velocity, pulsatility index) in the small arteries of the BG. Twenty-four healthy controls, twelve non-CAA CSVD patients, and five probable CAA patients underwent a 3 tesla [T] and 7T MRI-scan, and EPVS, arteries, and veins within the BG were manually segmented. Furthermore, the scans were co-registered. Six autopsy-cases were also assessed. In the BG, EPVS were significantly closer to and overlapped more frequently with arteries than with veins. Histological analysis showed a higher proportion of BG EPVS surrounding arteries than veins. Finally, the pulsatility index of BG arteries correlated with EPVS volume. Our results are in line with previous works and establish a pathophysiological relationship between arteries and EPVS, contributing to elucidating perivascular clearance routes in the human brain.
{"title":"Enlarged perivascular spaces in the basal ganglia are associated with arteries not veins.","authors":"Jan Oltmer, Hendrik Mattern, Julia Beck, Renat Yakupov, Steven M Greenberg, Jaco Jm Zwanenburg, Tine Arts, Emrah Düzel, Susanne J van Veluw, Stefanie Schreiber, Valentina Perosa","doi":"10.1177/0271678X241260629","DOIUrl":"10.1177/0271678X241260629","url":null,"abstract":"<p><p>Enlarged perivascular spaces (EPVS) are common in cerebral small vessel disease (CSVD) and have been identified as a marker of dysfunctional brain clearance. However, it remains unknown if the enlargement occurs predominantly around arteries or veins. We combined <i>in vivo</i> ultra-high-resolution MRI and histopathology to investigate the spatial relationship of veins and arteries with EPVS within the basal ganglia (BG). Furthermore, we assessed the relationship between the EPVS and measures of blood-flow (blood-flow velocity, pulsatility index) in the small arteries of the BG. Twenty-four healthy controls, twelve non-CAA CSVD patients, and five probable CAA patients underwent a 3 tesla [T] and 7T MRI-scan, and EPVS, arteries, and veins within the BG were manually segmented. Furthermore, the scans were co-registered. Six autopsy-cases were also assessed. In the BG, EPVS were significantly closer to and overlapped more frequently with arteries than with veins. Histological analysis showed a higher proportion of BG EPVS surrounding arteries than veins. Finally, the pulsatility index of BG arteries correlated with EPVS volume. Our results are in line with previous works and establish a pathophysiological relationship between arteries and EPVS, contributing to elucidating perivascular clearance routes in the human brain.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141306043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2023-11-07DOI: 10.1177/0271678X231210430
Yufan Wang, Stephen J Payne
The process by which cerebral blood flow (CBF) remains approximately constant in response to short-term variations in arterial blood pressure (ABP) is known as cerebral autoregulation. This classic view, that it remains constant over a wide range of ABP, has however been challenged by a growing number of studies. To provide an updated understanding of the static cerebral pressure-flow relationship and to characterise the autoregulation curve more rigorously, we conducted a comprehensive literature research. Results were based on 143 studies in healthy individuals aged 18 to 65 years. The mean sensitivities of CBF to changes in ABP were found to be 1.47 ± 0.71%/% for decreased ABP and 0.37 ± 0.38%/% for increased ABP. The significant difference in CBF directional sensitivity suggests that cerebral autoregulation appears to be more effective in buffering increases in ABP than decreases in ABP. Regression analysis of absolute CBF and ABP identified an autoregulatory plateau of approximately 20 mmHg (ABP between 80 and 100 mmHg), which is much smaller than the widely accepted classical view. Age and sex were found to have no effect on autoregulation strength. This data-driven approach provides a quantitative method of analysing static autoregulation that can be easily updated as more experimental data become available.
{"title":"Static autoregulation in humans.","authors":"Yufan Wang, Stephen J Payne","doi":"10.1177/0271678X231210430","DOIUrl":"10.1177/0271678X231210430","url":null,"abstract":"<p><p>The process by which cerebral blood flow (CBF) remains approximately constant in response to short-term variations in arterial blood pressure (ABP) is known as cerebral autoregulation. This classic view, that it remains constant over a wide range of ABP, has however been challenged by a growing number of studies. To provide an updated understanding of the static cerebral pressure-flow relationship and to characterise the autoregulation curve more rigorously, we conducted a comprehensive literature research. Results were based on 143 studies in healthy individuals aged 18 to 65 years. The mean sensitivities of CBF to changes in ABP were found to be 1.47 ± 0.71%/% for decreased ABP and 0.37 ± 0.38%/% for increased ABP. The significant difference in CBF directional sensitivity suggests that cerebral autoregulation appears to be more effective in buffering increases in ABP than decreases in ABP. Regression analysis of absolute CBF and ABP identified an autoregulatory plateau of approximately 20 mmHg (ABP between 80 and 100 mmHg), which is much smaller than the widely accepted classical view. Age and sex were found to have no effect on autoregulation strength. This data-driven approach provides a quantitative method of analysing static autoregulation that can be easily updated as more experimental data become available.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71482030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Spontaneous cerebral vasomotion, characterized by ∼0.1 Hz rhythmic contractility, is crucial for brain homeostasis. However, our understanding of vasomotion is limited due to a lack of high-precision analytical methods to determine single vasomotion events at basal levels. Here, we developed a novel strategy that integrates a baseline smoothing algorithm, allowing precise measurements of vasodynamics and concomitant Ca2+ dynamics in mouse cerebral vasculature imaged by two-photon microscopy. We identified several previously unrecognized vasomotion properties under different physiological and pathological conditions, especially in ischemic stroke, which is a highly harmful brain disease that results from vessel occlusion. First, the dynamic characteristics between SMCs Ca2+ and corresponding arteriolar vasomotion are correlated. Second, compared to previous diameter-based estimations, our radius-based measurements reveal anisotropic vascular movements, enabling a more precise determination of the latency between smooth muscle cell (SMC) Ca2+ activity and vasoconstriction. Third, we characterized single vasomotion event kinetics at scales of less than 4 seconds. Finally, following pathological vasoconstrictions induced by ischemic stroke, vasoactive arterioles entered an inert state and persisted despite recanalization. In summary, we developed a highly accurate technique for analyzing spontaneous vasomotion, and our data suggested a potential strategy to reduce stroke damage by promoting vasomotion recovery.
{"title":"High-resolution vasomotion analysis reveals novel arteriole physiological features and progressive modulation of cerebral vascular networks by stroke.","authors":"Yi-Yi Zhang, Jin-Ze Li, Hui-Qi Xie, Yu-Xiao Jin, Wen-Tao Wang, Bingrui Zhao, Jie-Min Jia","doi":"10.1177/0271678X241258576","DOIUrl":"10.1177/0271678X241258576","url":null,"abstract":"<p><p>Spontaneous cerebral vasomotion, characterized by ∼0.1 Hz rhythmic contractility, is crucial for brain homeostasis. However, our understanding of vasomotion is limited due to a lack of high-precision analytical methods to determine single vasomotion events at basal levels. Here, we developed a novel strategy that integrates a baseline smoothing algorithm, allowing precise measurements of vasodynamics and concomitant Ca<sup>2+</sup> dynamics in mouse cerebral vasculature imaged by two-photon microscopy. We identified several previously unrecognized vasomotion properties under different physiological and pathological conditions, especially in ischemic stroke, which is a highly harmful brain disease that results from vessel occlusion. First, the dynamic characteristics between SMCs Ca<sup>2+</sup> and corresponding arteriolar vasomotion are correlated. Second, compared to previous diameter-based estimations, our radius-based measurements reveal anisotropic vascular movements, enabling a more precise determination of the latency between smooth muscle cell (SMC) Ca<sup>2+</sup> activity and vasoconstriction. Third, we characterized single vasomotion event kinetics at scales of less than 4 seconds. Finally, following pathological vasoconstrictions induced by ischemic stroke, vasoactive arterioles entered an inert state and persisted despite recanalization. In summary, we developed a highly accurate technique for analyzing spontaneous vasomotion, and our data suggested a potential strategy to reduce stroke damage by promoting vasomotion recovery.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141183720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01Epub Date: 2024-08-05DOI: 10.1177/0271678X241254676
Jurgen Ahr Claassen
Advances in imaging techniques have transformed our understanding of cerebral autoregulation. Older imaging techniques provided measurements of cerebral blood flow (CBF) that reflected the average CBF over a window of 10-20 minutes. A key finding, dating back to 1959, was that CBF remained more or less stable over a remarkably wide range of changes in blood pressure. Modern techniques can measure changes in CBF within the time frame of a heartbeat. They have revealed, paradoxically, a remarkable instability of CBF. This commentary attempts to reconcile these seemingly contradictory observations.
{"title":"Shifting concepts of autoregulation: Commentary to 'Static autoregulation in humans'.","authors":"Jurgen Ahr Claassen","doi":"10.1177/0271678X241254676","DOIUrl":"10.1177/0271678X241254676","url":null,"abstract":"<p><p>Advances in imaging techniques have transformed our understanding of cerebral autoregulation. Older imaging techniques provided measurements of cerebral blood flow (CBF) that reflected the average CBF over a window of 10-20 minutes. A key finding, dating back to 1959, was that CBF remained more or less stable over a remarkably wide range of changes in blood pressure. Modern techniques can measure changes in CBF within the time frame of a heartbeat. They have revealed, paradoxically, a remarkable instability of CBF. This commentary attempts to reconcile these seemingly contradictory observations.</p>","PeriodicalId":15325,"journal":{"name":"Journal of Cerebral Blood Flow and Metabolism","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}